We are studying the effects of marihuana on male endocrine, reproductive and sexual functions. Our objective is to define the effects of psychoactive and non-psychoactive constituents of marihuana on the pituitary, the testes and on male sexual behavior and to determine the mechanisms of these effects. During the next four years, we will address the mechanism of action of delta-9-tetrahydrocannabinol (THC) on male copulatory behavior and study the effects of perinatal or adult administration of THC, cannabinol (CBN) and cannabidiol (CBD) on hypothalamic and pituitary function. More specifically, we will test our hypothesis that the neurotransmitter-mediated alterations in the release of gonadotropin releasing hormone (GnRH) are responsible for the effects of THC on sexual behavior. We will also examine the effects of THC, CBN and CBD on the function of hypothalamic catecholaminergic neurons which are known to control the release of gonadotropins and prolactin from the anterior pituitary. These studies will be conducted in male rats and mice and will involve oral administration of different components of marihuana, measurements of levels and turnover rates of hypothalamic neurotransmitters, incubations of hypothalami and anterior pituitaries, determinations of GnRH receptors in the pituitary and radioimmunoassay measurements of blood levels of pituitary and testicular hormones. Copulatory behavior will be tested in the presence of ovariectomized females brought into sexual receptivity by estrogen and progesterone injections. Further studies will involve administration of blockers and precursors of hypothalamic neurotransmitters in an attempt to mimic or prevent cannabinoid effects on behavior and pituitary function as well as cuts, lesions and stimulations of specific sites in the brain aimed at localizing the sites of cannabinoid action and the anatomical pathways of their effects.